Successful Outcome With a ???Quintuple Approach??? Of Posttransplant Lymphoproliferative Disorder

Schaar, C. G.; Pijl, J.W. van der; Hoek, Bart van; Fijter, Johan W. de; Veenendaal, R.A.; Kluin, Philip M.; Krieken, J.H.J.M. van; Hekman, Annemarie; Terpstra, Wim; Willemze, R.; Kluin-Nelemans, Hanneke C.

doi:10.1097/00007890-200101150-00008

Cited by 41 publications

(24 citation statements)

References 26 publications

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“…Based on the correlation in humans and the experimental data in SCID mice, high-dose i.v. gamma globulin, containing high levels of anti-EBV Abs, has been incorporated into some combined treatment protocols for posttransplant lymphoproliferative disorders following solid organ transplant (48,50). However, Ig therapy is not widely used in the prevention and treatment of posttransplant lymphoproliferative syndromes, and only recently have clinical trials been initiated to establish the efficacy of anti-viral Ab therapy (48).…”

Section: Discussionmentioning

confidence: 99%

Antibody-Mediated Control of Persistent γ-Herpesvirus Infection

Kim

Flaño

Woodland

et al. 2002

The Journal of Immunology

127

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The human γ-herpesviruses, EBV and Kaposi’s sarcoma-associated herpesvirus, establish life-long latency and can reactivate in immunocompromised individuals. T cells play an important role in controlling persistent EBV infection, whereas a role for humoral immunity is less clear. The murine γ-herpesvirus-68 has biological and structural similarities to the human γ-herpesviruses, and provides an important in vivo experimental model for dissecting mechanisms of immune control. In the current studies, CD28−/− mice were used to address the role of Abs in control of persistent murine γ-herpesvirus-68 infection. Lytic infection was controlled in the lungs of CD28−/− mice, and latency was maintained in B cells at normal frequencies. Although class-switched virus-specific Abs were initially generated in the absence of germinal centers, titers and viral neutralizing activity rapidly waned. T cell depletion in CD28−/− mice with compromised Ab responses, but not in control mice with intact Ab responses, resulted in significant recrudescence from latency, both in the spleen and the lung. Recrudescence could be prevented by passive transfer of immune serum. These data directly demonstrate an important contribution of humoral immunity to control of γ-herpesvirus latency, and have significant implications for clinical intervention.

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Section: Discussionmentioning

confidence: 99%

Antibody-Mediated Control of Persistent γ-Herpesvirus Infection

Kim

Flaño

Woodland

et al. 2002

The Journal of Immunology

127

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“…IgG therapy (53)(54)(55)(56). Especially in the case of neurotropic viruses, Abs have been shown to limit or prevent virus spread to the CNS system or restrict virus expression (57)(58)(59)(60).…”

Section: Different Strategies Leading To Similar Outcomes: Mmtv Vs Ebvmentioning

confidence: 99%

The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development

Finke

Luther²,

Acha‐Orbea³

2002

Proc. Natl. Acad. Sci. U.S.A.

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Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers and a lifelong neutralizing Ab response. We show that removal of the draining lymph node after establishment of the germinal center reaction led to complete loss of neutralizing Abs despite comparable infection levels in peripheral lymphocytes. Importantly, in the absence of neutralization, only the exocrine organs mammary gland, salivary gland, pancreas, and skin showed strikingly increased infection, resulting in accelerated mammary tumor development. Induction of stronger neutralization did not influence chronic infection levels of peripheral lymphoid organs but strongly inhibited mammary gland infection and virus transmission to the next generation. Taken together, we provide evidence that a tight equilibrium in virus neutralization allows limited infection of exocrine organs and controls cancer development in susceptible mouse strains. These experiments show that a strong neutralizing Ab response induced after infection is not able to control lymphoid MMTV infection. Strong neutralization, however, is capable of blocking amplification of mammary gland infection, tumor development, and virus transmission to the next generation. The results also indicate a role of neutralization in natural resistance to MMTV infection.

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“…4 There is ample evidence that an adoptive immunotherapy approach with transfer of lymphocytes or EBV-specific CTLs of donor origin is effective as prophylaxis and/or treatment of EBV-related PTLD in recipients of T-cell-depleted BMT [5][6][7][8] ; data have shown that anti-CD20 monoclonal antibody can be an equally useful therapeutic strategy when donor-derived EBV CTLs are not available. 9,10 Conversely, treatment of PTLD in patients receiving organ allografts who fail to respond to reduction or discontinuation of immunosuppression, [11][12][13] is still controversial. Antiviral drugs, 12 ␣ interferon, [12][13][14] anti-Bcell monoclonal antibodies, 12,15 and chemotherapy 13,16,17 have all been used and reported to induce remission in selected cases, and, as described for BMT recipients, also in the setting of SOT the use of anti-CD20 has proved effective in resolving established PTLD.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 Conversely, treatment of PTLD in patients receiving organ allografts who fail to respond to reduction or discontinuation of immunosuppression, [11][12][13] is still controversial. Antiviral drugs, 12 ␣ interferon, [12][13][14] anti-Bcell monoclonal antibodies, 12,15 and chemotherapy 13,16,17 have all been used and reported to induce remission in selected cases, and, as described for BMT recipients, also in the setting of SOT the use of anti-CD20 has proved effective in resolving established PTLD. 18 Notwithstanding the 50% to 85% remission rate attained by the reported therapeutic approaches, frequent complications such as rejection, toxicity, and other infectious pathologies heavily compromise graft and host survival; moreover, overall mortality in patients with unresponsive PTLD remains high.…”

Section: Introductionmentioning

confidence: 99%

Infusion of autologous Epstein-Barr virus (EBV)–specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication

Comoli

Labirio

Basso

et al. 2002

Blood

233

159

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Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorders (PTLDs) are a well-recognized complication of immunosuppression in solid organ transplant recipients. The reported therapeutic approaches are frequently complicated by rejection, toxicity, and other infectious pathologies, and overall mortality in patients with unresponsive PTLD remains high. Thus, low-toxicity treatment options or, preferably, some form of prophylactic/preemptive intervention are warranted to improve PTLD outcome in this setting. We assessed whether transfer of EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from the peripheral blood of allograft recipients receiving immunosuppression could increase EBV-specific killing in vivo without augmenting the probability of graft rejection. Autologous EBV-specific CTLs were generated for 23 patients who were identified as being at risk of developing PTLD through the finding of elevated EBV DNA load. Of the 23 patients, 7 received 1 to 5 infusions of EBV-specific CTLs. CTL transfer was well tolerated, and none of the patients showed any evidence of rejection. An increase of the EBV-specific cytotoxicity was observed after infusion, notwithstanding continuation of immunosuppressive therapy. EBV DNA levels had a 1.5-to 3-log decrease in 5 patients, whereas in the other 2 graft recipients CTL transfer had no apparent stable effect on EBV load. Our data suggest that the infusion of autologous EBVspecific CTLs obtained from peripheral blood mononuclear cells recovered at the time of viral reactivation is able to augment virus-specific immune response and to reduce viral load in organ transplant recipients. This approach may, therefore, be safely used as prophylaxis of EBV-related lymphoproliferative disorders in these patients, following a strategy of preemptive therapy guided by EBV DNA levels. (Blood. 2002;99: 2592-2598

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Successful Outcome With a ???Quintuple Approach??? Of Posttransplant Lymphoproliferative Disorder

Abstract: This combined approach resulted in a favorable outcome in patients with high risk monoclonal PTLD after solid organ transplantation.

Cited by 41 publications

References 26 publications

Antibody-Mediated Control of Persistent γ-Herpesvirus Infection

Antibody-Mediated Control of Persistent γ-Herpesvirus Infection

The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development

Infusion of autologous Epstein-Barr virus (EBV)–specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication

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